Long-Term Safety of In Utero Exposure to Anti-TNFα Drugs for the Treatment of Inflammatory Bowel Disease: Results from the Multicenter European TEDDY Study.

OBJECTIVES: The long-term safety of exposure to anti-tumor necrosis factor (anti-TNFα) drugs during pregnancy has received little attention. We aimed to compare the relative risk of severe infections in children of mothers with inflammatory bowel disease (IBD) who were exposed to anti-TNFα drugs in utero with that of children who were not exposed to the drugs. METHODS: Retrospective multicenter cohort study. Exposed cohort: children from mothers with IBD receiving anti-TNFα medication (with or without thiopurines) at any time during pregnancy or during the 3 months before conception. Non-exposed cohort: children from mothers with IBD not treated with anti-TNFα agents or thiopurines at any time during pregnancy or the 3 months before conception. The cumulative incidence of severe infections after birth was estimated using Kaplan-Meier curves, which were compared using the log-rank test. Cox-regression analysis was performed to identify potential predictive factors for severe infections in the offspring. RESULTS: The study population comprised 841 children, of whom 388 (46%) had been exposed to anti-TNFα agents. Median follow-up after delivery was 47 months in the exposed group and 68 months in the non-exposed group. Both univariate and multivariate analysis showed the incidence rate of severe infections to be similar in non-exposed and exposed children (1.6% vs. 2.8% per person-year, hazard ratio 1.2 (95% confidence interval 0.8-1.8)). In the multivariate analysis, preterm delivery was the only variable associated with a higher risk of severe infection (2.5% (1.5-4.3)). CONCLUSIONS: In utero exposure to anti-TNFα drugs does not seem to be associated with increased short-term or long-term risk of severe infections in children.

Current concepts on microscopic colitis: evidence-based statements and recommendations of the Spanish Microscopic Colitis Group.

BACKGROUND: Microscopic colitis (MC) is an underdiagnosed inflammatory bowel disease. AIM: To develop an evidence-based clinical practice guide on MC current concepts. METHODS: Literature search was done on the Cochrane Library, EMBASE and MEDLINE electronic databases, which were consulted covering the period up until March 2015. Work groups were selected for each of the reviewed topics, with the purpose of drafting the initial statements and recommendations. They subsequently underwent a voting process based on the Delphi method. Each statement/recommendation was accompanied by the result of the vote the level of evidence, and discussion of the corresponding evidence. The grade of recommendation (GR) using the GRADE approach was established for diagnosis and treatment recommendations. RESULTS: Some key statements and recommendations are: advancing age increases the risk of developing MC, mainly in females. The symptoms of MC and IBS-D may be similar. If MC is suspected, colonoscopy taking biopsies is mandatory. Treatment with oral budesonide is recommended to induce clinical remission in patients with MC. Oral mesalazine is not recommended in patients with collagenous colitis for the induction of clinical remission. The use of anti-TNF-alpha drugs (infliximab, adalimumab) is recommended for the induction of remission in severe cases of MC that fail to respond to corticosteroids or immunomodulators, as an alternative to colectomy. CONCLUSIONS: This is the first consensus paper on MC based on GRADE methodology. This initiative may help physicians involved in care of these patients in taking decisions based on evidence.

Thiopurine methyl-transferase activity and azathioprine metabolite concentrations do not predict clinical outcome in thiopurine-treated inflammatory bowel disease patients.

BACKGROUND: Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. AIM: To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. METHODS: Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. RESULTS: A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. CONCLUSIONS: Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug's dose was identified.

Diffuse cavernous hemangioma of the rectum: an atypical cause of rectal bleeding.

OBJECTIVE: cavernous hemangioma of the rectosigmoid colon is a rare disease, with no more than 200 cases reported in the literature. The rectosigmoid is the most common site of this disease in the gastrointestinal tract. CASE REPORT: we report the case of a 31-year-old male with recurrent episodes of rectal bleeding, who was finally diagnosed of diffuse cavernous hemangioma of the rectum. The tumor, of 12 x 10 x 9 cm in size, occupied the rectum to the margin of the anal sphincter. A surgical procedure was ruled out because of the inability to carry out a safe anastomosis while preserving anal sphincters. DISCUSSION: rectal hemangiomas are less frequent vascular malformations. The clinical presentation of a cavernous hemangioma of the rectum is usually acute, recurrent or chronic rectal bleeding. Other symptoms stem from the possible compression or invasion of adjacent structures, such as lumbar or perianal pain, metrorrhage, hematuria, etc. This diagnosis is commonly made in younger patients. Colonoscopy is without doubt the diagnostic technique of choice, and it allows to establish the localization, morphology, and total extension of the lesion; its characteristic image is a red-purplish nodule with great vascular congestion. According to the opinion of most authors, biopsy is not advisable during colonoscopy, since imaging techniques are sufficient for an accurate diagnosis, and the risk of bleeding while manipulating this lesion is not negligible. Computed tomography and particularly magnetic resonance imaging, given their high precision to delimit the lesion and its relations to adjacent structures, are imaging studies that are mandatory before surgical treatment. Other techniques such as selective angiography, barium enema, gastrointestinal transit, and upper-tract endoscopy may be supplementary and help locate more lesions along the gastrointestinal tract. Failure to recognize the exact diagnosis and extent of diffuse cavernous hemangioma may lead to failed surgical treatment and severe complications. Complete surgical excision of the lesion with a sphincter-saving procedure is the primary mode of treatment: conservative proctectomy with coloanal anastomosis.

Prevalence and antimicrobial-resistance of S. pneumoniae and S. pyogenes in healthy children in the region of Madrid.

UNLABELLED: Streptococcus pneumoniae and Streptococcus pyogenes are common agents of respiratory or ORL pathology. Pneumococcus sensitivity has progressively decreased to penicillin and other antimicrobial agents, mainly in south of Europe, but this resistance report can be erroneous by a selection bias, because they sampled only hospital cases. OBJECTIVES: To determine the prevalence, antimicrobial susceptibility and risk factors of S. pneumoniae and S. pyogenes in healthy children under 5 years of age who go to infant school. SUBJECT AND METHODS: Cross sectional study in six infant schools. An epidemiological inquiry (risk factors of carrier state) was filled out and a nasopharyngeal specimen was taken from each child, S. pneumoniae and S. pyogenes were identified and antimicrobial tests were performed. RESULTS: We have studied 156 children with a mean age of 2.24 (standard deviation (S.D.), 0.85) and 58% have been treated with antibiotic in the last 3 months. The prevalence of S. pneumoniae or S. pyogenes were 12.2 and 5.1%, respectively. S. pyogenes only was isolated in two schools. Age was associated with S. pyogenes carrier but the rest of studied factors have no statistical significance with both microorganisms. All the S. pneumoniae showed resistance to one or more antibiotic (mainly to clavunate-amoxycillin: 94.7%), while S. pyogenes only was resistant to clavunate-amoxycillin. CONCLUSION: Healthy children (0-4 years) with antibiotherapy in last 3 months have a great frequency of resistant S. pneumoniae. It is necessary to reduce the antibiotic use at home (Medical education).